Protective effects of N-acetylcysteine on hypothermic ischemia-reperfusion injury of rat liver

✍ Scribed by Dr Hiroshi Nakano; Karim Boudjema; Eliane Alexandre; Pierre Imbs; Marie Pierre Chenard; Philippe Wolf; Jacques Cinqualbre; Daniel Jaeck

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 858 KB
• Volume: 22
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840220225

✦ Synopsis

We investigated whether intraportal injection of 150 mgkg N-acetylcysteine (NAC) into rats reduced hepatic ischemia-reperfusion injury after 48 hours of cold storage and 2 hours of reperfusion. The organ was isolated and perfused to evaluate liver function. The control group received an intraportal injection of 5% dextrose. NAC increased L-cysteine concentrations 15 minutes after injection (1.29 t 0.11 pmoVg vs. 2.68 t 0.4 pmoVg, P < .05). However, neither treatment modified glutathione liver concentrations relative to preinjection values. After 48 hours of cold storage and 2 hours of reperfusion, livers from NAC-treated rats produced larger amounts of bile than those in the control group (5.04 i-1.92 vs. 0.72 -+ 0.37 p u g liver; P < .05), and showed a significant reduction in liver injury, as indicated by reduced release of lactate dehydrogenase (679.4 5 174.4 vs. 1891.3 t 268.3 IUWg; P < .Ol), aspartate transaminase (AST) (13.94 23.5 vs. 38.75 IUWg; P < .Ol), alanine transaminase (ALT) (14.92 t 4.09 vs. 45.91 2 10.58 IUWg; P < .05), and acid phosphatase, a marker of Kupffer cell injury (344.4 t 89.6 vs. 927.3 t 150.8 WWg; P < .01) in the perfusate.

Reduced glutathione concentrations in the perfusate were similar in the two groups (805 i-69 vs. 798 2 252 nmoWg), whereas oxidized glutathione (GSSG) concentrations were higher in the control group (967 t 137 vs. 525 2 126 nmoWg P < .05). Reduced glutathione (GSH) concentrations in liver tissue collected at the end of perfusion were significantly higher in the NAG group (7.3 t 0.9 vs. 4.1 -C 1.0 pmoVg; P < .05). The protective effect of NAC on cold ischemia-reperfusion liver injury persisted when animals were pretreated with buthionine sulfoximine (BSO), a specific inhibitor of glutathione synthesis.